Synthesis and reactivity of a cyclopentadienyl-indenyl ligand ring-coupled by a chiral bridge derived from ethyl (S)-(-) lactate.

In order to prepare a new unsymmetrical chiral ligand, C9H7CH(CH3)CH2C5H5, with an indenyl moiety connected to a cyclopentadienyl unit by a chiral ethylene bridge, we reacted the optically active tosylate 4, derived from ethyl (S)-(-) lactate, with LiCp. The only product resulting from this reaction was an optically active spirocyclopropane 6 obtained with a high diastereoselectivity (81.8% de). We also observed that, when the reduction of the ethyl indene lactate 2 was realized with an excess of LiAlH4 in Et2O under reflux, spirocyclopropane 6 was obtained in high yield with the same diastereoselectivity. When tosylate 4 was reacted with MgCp2, in place of LiCp, ligand 5 was obtained in good yield as a mixture of two double-bond isomers of the Cp unit. Ligand 5 was fully structurally characterized after conversion into transition monometallic complexes such as C9H7CH(CH3)CH2η(5)-C5H4Mo(CO)3Me 7 and C9H7CH(CH3)CH2η(5)-C5H4Rh(COD) 9, in which the indene moiety was kept intact due to the difference in reactivity of the indenyl moiety with respect to the cyclopentadienyl unit. An attempt to prepare a heterobimetallic complex from the sodium indenide salt of 7 and [RhCl(COD)]2, afforded a rhodium cyclopentadienyl complex 9, resulting from a metal exchange reaction with loss of the molybdenum part initially coordinated to the Cp unit, and conservation of the optical purity. An homobimetallic rhodium complex 10 could be prepared by deprotonation of ligand 5 with TlOEt, followed by quenching with [RhCl(COD)]2. The bis-rhodium complex 10 is obtained as a mixture of two diastereoisomers 10a and 10b with respect to the planar chirality of the indenyl ring system, with a good diastereoisomeric excess de = 70%. The structures of both complexes 9 and major (pS)-diastereoisomer 10a were determined by single crystal X-ray diffraction.

Diagnostic triage and the role of natriuretic peptide testing and echocardiography for suspected heart failure: an appropriateness ratings evaluation by UK GPs.

BACKGROUND: Some UK GPs are acquiring access to natriuretic peptide (NP) testing or echocardiography as diagnostic tests for heart failure. This study developed appropriateness ratings for the diagnostic application of these tests in routine general practice. AIM: To develop appropriateness ratings for the diagnostic application of NP testing or echocardiography for heart failure in general practice. DESIGN AND SETTING: An appropriateness ratings evaluation in UK general practice. METHOD: Four presenting symptoms (cough, bilateral ankle swelling, dyspnoea, fatigue), three levels of risk of cardiovascular disease (low, intermediate, high), and dichotomous categorisations of cardiovascular/chest examination and electrocardiogram result, were used to create 540 appropriateness scenarios for patients in whom NP testing or echocardiography might be considered. These were rated by a 10-person expert panel, consisting of GPs and GPs with specialist interests in cardiology, in a two-round RAND Appropriateness Method. RESULTS: Onward referral for NP testing or echocardiography was rated as an appropriate next step in 217 (40.2%) of the 540 scenarios; in 194 (35.9%) it was rated inappropriate. The ratings also show where NP testing or echocardiography were ranked as equivalent next steps and when one test was seen as the more appropriate than the other. CONCLUSION: NP testing should be the routine test for suspected heart failure where referral for diagnostic testing is considered appropriate. An abnormal electrocardiogram status makes referral to echocardiography an accompanying, or more appropriate, next step alongside NP testing, especially in the presence of dyspnoea. Abnormal NP testing should subsequently be followed up with referral for echocardiography.

The medical history as a diagnostic technology.

The medical history is a powerful diagnostic technology. However, in seeking to establish an appropriate balance between the history and the other diagnostic modalities more explicit consideration must be given to the performance characteristics of the medical history. Building on recent work undertaken in the UK and elsewhere in Europe it is now feasible to develop a library of setting-specific likelihood ratios and kappa statistics for key elements of the medical history. Of particular importance to those working in primary care, statistically adjusted combinations of information from the medical history can be generated; furnishing clinicians with likelihood ratios of significant magnitudes. It is suggested that developing a more rational approach to the use of the medical history could lead to improvements in diagnostic efficiency and effectiveness, with benefits for individual patient care in addition to the overall NHS budget. When diagnosis is viewed as a processing pathway founded on a robust medical history, it becomes clear than in some situations investigations may become unnecessary and, in other circumstances, their impact will be enhanced.

Statistical methods in epidemiology. VIII. On the use of likelihood ratios for diagnostic testing with an application to general practice.

PURPOSE: An array of statistical methods is available for 2 x 2 contingency table analysis. These include odds ratios, reliability coefficients and the Chi-squared test. This paper continues the '2 x 2' theme but extends it to look at diagnostic testing. The setting is primary care, the disease is urological cancer. METHOD: Several statistical indices are discussed to measure diagnostic efficiency; these include sensitivity, specificity and the likelihood ratio. The latter can be converted into a flexible 'weight of evidence', which is equivalent to the naive Bayes' discriminant. RESULTS: The utility of the naive Bayes' discriminant is illustrated in a primary care setting. CONCLUSION: The naive Bayes' discriminant has proved to be the most durable of statistical discriminants in medical diagnosis. The reason for its durability is ease of use. Despite a concern about independence, it remains a popular choice as a diagnostic aid.

Clinical management. Close encounters.

Primary care trusts are increasingly using 'local enhanced service' programmes to target excluded groups, according to new research. One in seven PCTs were using an LES for asylum seekers and other examples include homelessness, learning disabilities and work with young people. Other PCTs are using LESs to shift work from secondary to primary care via referral management incentive schemes, while one in five had set up an LES-based phlebotomy service.